The objective of this proposal is to investigate coherent optical technology for monitoring glucose concentration. The proposed advances take the advantage of the intrinsic optical path selectivity of optical coherence tomography (OCT), a recently developed technology for quantitative, non-invasive tissue sensing and imaging based on low-coherence interferometry. Methods for monitoring tissue index of refraction, scattering and polarization changes are proposed which feature explicit control over sampled tissue path length. The specific aims of the proposal are to: 1) test the feasibility of three new concepts for micron-scale path-length-resolved, non-invasive optical glucose sensing based upon adaptations of optical coherence tomography (OCT), 2) correlate the measurements with actual glucose concentrations in simple and increasingly complex tissue fluid models, as well as in human volunteers undergoing glucose challenge tests. Each of the proposed technical approaches is completely non-invasive, requiring no withdrawal of blood or subcutaneous fluid and do not require disposable supplies or re-stocking of enzymes.